The objective of this project is to explore the mechanisms regulating hepatic synthesis of the acute phase protein C-reactive protein (CRP) during periods of inflammation and tissue necrosis and during recovery periods. We will attempt to demonstrate the presumed circulating mediator responsible for increased hepatic C-reactive protein synthesis in inflammation, to characterize it and to determine its concentration in blood. The mechanisms leading to formation of such a mediator will be explored. We will investigte hepatic cellular population dynamics during the period of rapid increase in rate of CRP production: does increased production result from increased output by a fixed number of cells or from an increase in the number of cells producing CRP? If the latter, does the increase in number of cells result from replication or recruitment of CRP producing cells? We would like to determine whether hepatocytes of Kupffer cells are the CRP-producing cells. The mechanisms leading to cessation of CRP synthesis following recovery from inflammation will be studied to determine if repressor mechanisms are actively induced. Catabolism of CRP will be studied to determine mechanisms involved in removal of CRP from blood and whether catabolic rate differs in normal and inflamed animals.